Cycloaddition between nitriles and

Another general approach to the synthesis of fluorinated 1,2,4-oxadiazoles is based on the [3-1-2] cycloaddition between nitriles and nitrile oxides (each component of the reaction can contain the fluorinated moiety). Cycloaddition of the trifluoroace-tonitrile oxide 37 produced the 3-trifluoromethyl-5-phenyl derivative 38 (Ar=Ph) (Scheme 11) [21]. Unfortunately, aliphatic nitriles such as the butyronitrile do not undergo cycloaddition into the oxadiazole derivative [21]. 

The method involving cycloaddition between nitriles and nitrile oxides has also been employed for the synthesis of complex systems precursors of polymeric materials. For example, terephthaldinitrile oxide 39 was reacted with RpCN (Scheme 12) to give representative oxadiazole 40. In the case of RF=nitrile-terminated polyper-fluoroalkylether chain, the presence of several nitrile pendants as curing sites can lead to further functionalized oligomers 41 [22],... 

Pyridine compounds 45 can also be produced by the NHC-Ni catalysed cycloaddition between nitriles 43 and diynes 44 (Scheme 5.13) [16]. The SIPr carbene was found to be the best ligand for the nickel complex in this reaction. The reaction required mild reaction conditions and low catalyst loadings, as in the case of cycloaddition of carbon dioxide. In addition to tethered aUcynes (i.e. diynes), pyridines were prepared from a 3-component coupling reaction with 43 and 3-hexyne 23 (Scheme 5.13). The reaction of diynes 44 and nitriles 43 was also catalysed by a combination of [Ni(COD)J, NHC salts and "BuLi, which generates the NHC-Ni catalyst in situ. The pyridines 45 were obtained with comparable... 

DFT studies of the intramolecular ene-like (or the so-called 1,3-dipolar ene) reaction between nitrile oxides and alkenes show that this reaction is a three-step process involving a stepwise carbenoid addition of nitrile oxide to form a bicyclic nitroso compound, followed by a retro-ene reaction of the nitrosocyclopropane intermediate. The competitive reactions, either the intramolecular [3 + 2] cycloaddition between nitrile oxides and alkenes or the intermolecular dimerization of nitrile oxides to form furoxans, can overwhelm the intramolecular 1,3-dipolar ene reaction if the tether joining the nitrile oxide and alkene is elongated, or if substituents such as trimethylsilyl are absent (425). 

Dipolar addition is closely related to the Diels-Alder reaction, but allows the formation of five-membered adducts, including cyclopentane derivatives. Like Diels-Alder reactions, 1,3-dipolar cycloaddition involves [4+2] concerted reaction of a 1,3-dipolar species (the An component and a dipolar In component). Very often, condensation of chiral acrylates with nitrile oxides or nitrones gives only modest diastereoselectivity.82 1,3-Dipolar cycloaddition between nitrones and alkenes is most useful and convenient for the preparation of iso-xazolidine derivatives, which can then be readily converted to 1,3-amino alcohol equivalents under mild conditions.83 The low selectivity of the 1,3-dipolar reaction can be overcome to some extent by introducing a chiral auxiliary to the substrate. As shown in Scheme 5-51, the reaction of 169 with acryloyl chloride connects the chiral sultam to the acrylic acid substrate, and subsequent cycloaddition yields product 170 with a diastereoselectivity of 90 10.84... 

Dipolar cycloaddition between azides and nitriles is also a well-established route to tetrazoles. If these two functional groups are closely located within one molecule, intramolecular cyclization can occur to yield fused tetrazoles. The present survey of the recent literature shows that this approach has also been successfully applied in some cases and led to the synthesis of novel ring systems belonging to this chapter. These results are depicted in Scheme 25. 

Oxazin-4-ones are obtained by cycloadditions between isocyanates and ketenes (Scheme 37). Routes to 1,3-oxazinium salts consist of 1,4-cycloadditions either between a,(3-unsaturated (3-chlorocarbonyl compounds and nitriles or between /V-acylimidoyl chlorides and alkynes. Tin(IV) chloride is an effective catalyst for both reactions (c/. Scheme 38). 

Oxazin-4-ones and -thiazin-4-ones are well represented in the chemical literature. Thiazin-4-ones can be synthesized from 1,3-oxazinium salts by the action of hydrogen sulfide and potassium carbonate (81H(15)85l) and oxazin-4-ones are obtained by cycloadditions between isocyanates and ketenes (Scheme 73), or alkynes (Scheme 74), or between nitriles and acylketenes (Scheme 75). Similarly diketene is often used and affords oxazin-4-ones by its reactions with imidates and cyanamides (Scheme 76) (80H(14)1333>. 

The 1,2,3-azadisiletidine 47 and 1,2,3-azadisiletine 48 are, in a formal sense, the products of a [2+2] cycloaddition reaction between nitriles and disilene (Scheme 20). It can be assumed that the latter is the crucial intermediate formed during the thermolysis of hexasubstituted cyclotrisilane <1995TL8187>. 

A Rh2(OAc)4-catalyzed cycloaddition between nitrile 202 and dimethyl diazomalonate 203 gave oxazole 204 which was further elaborated into the side-chain of marine macrolide leucascandrolide A (Scheme 59) <2002JA13670>. 

Oh and co-workers utilized nitrile oxide cycloaddition chemistry for the preparation of 4-oxo-2-alkenylphosphonates 247 by y-acylation of allyhc phosphonates 244 (Scheme 58) [158,159]. Regioselective dipolar cycloaddition between nitrile oxides obtained from nitroalkanes 13 and allylic phosphonates 244 serving as dipolarophiles provided phosphonate-containing 2-isoxazolines 245 in good yields. Isoxazolines 245 upon LDA-mediated ring cleavage followed by hydrolysis of the corresponding oximes 246 yielded 4-oxo-2-alkenylphosphonates 247. 

From the cycloaddition reaction standpoint, the photo-generated reactive species suitable for both 1,3-dipolar cycloaddition reactions and Diels-Alder reactions have been studied in the literature. In this review, we will focus our discussion on four cycloaddition reactions (1) 1,3-dipolar cycloaddition between aUcenes and photogenerated nitrile imines (2) 1,3-dipolar cycloaddition between aUcenes and photogenerated nitrile ylides (3) photoinduced hetero Diels-Alder reactions and (4) photoinduced strain promoted azide-alkyne cycloaddition (Scheme 3). It is... 

Recently, Renaud and coworkers reported a new, simple, and air-stable iron(II) complex pre-catalyst catalyzed synthesis of substituted pyridines via [2 -F 2 -F 2] cycloaddition between diynes and nitrile derivatives [50]. Alkyl-, aryl-, and vinyl nitriles could all be applied functionalized pyridines can be produced in high yields without any pre-reduction of the catalyst (Scheme 3.22). 

The synthesis of chiral racemic atropisomeric pyridines by cobalt-catalyzed [2 + 2 + 2] cycloaddition between diynes and nitriles was reported in 2006 by Hrdina et al. using standard CpCo catalysts [CpCo(CO)2, CpCo(C2H4)2, CpCo(COD)] [34], On the other hand, chiral complexes of type II were used by Gutnov et al. in 2004 [35] and by Hapke et al. in 2010 [36] for the synthesis of enantiomerically enriched atropisomers of 2-arylpyridines (Scheme 1.18). This topic is described in detail in Chapter 9. It is noteworthy that the 2004 paper contains the first examples of asymmetric cobalt-catalyzed [2 - - 2 - - 2] cycloadditions. At that time, it had been preceded by only three articles dealing with asymmetric nickel-catalyzed transformations [37]. Then enantioselective metal-catalyzed [2 -i- 2 - - 2] cycloadditions gained popularity, mostly with iridium- and rhodium-based catalysts, as shown in Chapter 9. 

Since 1901, conventional synthesis of 5-substituted l//-tetrazoles has been reported to proceed via [3-1-2] cycloaddition between azide and nitriles. Drawbacks from this procedure are the use of expensive and toxic azide, highly moisture-sensitive reaction conditions, strong Lewis acids, and hydrazoic acid. 

Similar cycloadditions between thiirene dioxides and 1,3-dipoles generated in situ give heterocycles which result from either loss of sulfur dioxide or from the three-membered ring opening of the initially formed adduct (e.g. 174). Such cycloadditions with nitrilium imides (173a) and nitrile ylids (173b) are illustrated in equation 69175. 

A plausible mechanism for the [2+2+2] cycloaddition reactions between diynes and heterocumnlenes (or nitriles) is shown in Scheme 5.16. Initially [2+2] oxidative addition of one alkyne and the heterocnmnlene (or nitrile) forms the five-mem-bered intermediate 54 compound 55 is formed after the insertion of the second alkyne and finally the seven-membered compound 55 undergoes reductive elimination to afford the prodnct 56 and regenerate the Ni(0) catalyst. 

An interesting strategy for the synthesis of pyrrolizidines and indolizidines has been developed by Brandi and co-workers. Cycloaddition between nitrones or nitrile oxides with methylenecyclopropanes generates strained tricyclic spiro compounds, which are prone toward further transformations, such as rearrangement, ring opening, and new ring closure (Scheme 10.17).116... 

In the scope of this subsection, competitive 1,3-cycloaddition of nitrile oxides to carbon-carbon and carbon-heteroatom multiple bonds are of special interest. Competition between carbon-carbon and carbon-nitrogen double bonds in... 

Rhenium-catalyzed [3 + 2]-cycloaddition reactions between imines and nitriles affording indene derivatives were reported by Kuninobu et al. these authors demonstrated that only 3 mol.% of [ReBr(CO)3(THF)]2 allowed the transformation to proceed in high yield (Scheme 69).311... 

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